Agmatine inhibits morphine-induced locomotion sensitization and morphine-induced changes in striatal dopamine and metabolites in rats.
Eur Neuropsychopharmacol
; 17(12): 790-9, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17604969
ABSTRACT
The effects of agmatine on morphine-induced locomotion sensitization and morphine-induced changes in extracellular striatal dopamine (DA) and DA metabolites were studied. The locomotor response to morphine challenge (3 mg/kg, s.c.) was enhanced in rats 3 days after repeated morphine administration, indicating development of locomotion sensitization. In vivo microdialysis demonstrated a significant increase in striatal basal levels of the DA metabolites DOPAC and HVA, but not in DA itself, and an increase in DA response to morphine challenge in rats 3 days after withdrawal. Agmatine (1, 10, 80 mg/kg) inhibited morphine-induced locomotion sensitization and the changes in DA noted above. Idazoxan attenuated the effects of agmatine on locomotion, suggesting that the effects are mediated by imidazoline receptors. In addition, repeated morphine also increased the expression of tyrosine hydroxylase mRNA in the VTA after 4 days of morphine pretreatment, while decreasing the expression of dynorphin mRNA at 3 days after withdrawal. Agmatine inhibited morphine-induced changes in dynorphin, but not in tyrosine hydroxylase mRNA expression. These data suggest that agmatine, likely by activating imidazoline receptors, inhibits morphine-induced locomotion sensitization and morphine-induced changes in extracellular DA and in dynorphin expression. Thus, agmatine deserves further study as an anti-opioid medication.
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Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Corpo Estriado
/
Agmatina
/
Locomoção
/
Morfina
/
Entorpecentes
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article